A novel immuno–positron-emission tomography (immunoPET) imaging agent targeting GPC3 demonstrated high sensitivity and specificity in detecting GPC3-positive hepatocellular carcinoma (HCC) tumors, including those under 1 cm, according to the results of a pilot clinical study presented at the Society of Nuclear Medicine and Molecular Imaging 2025 Annual Meeting (Abstract 252173).
PET/magnetic resonance (MR) scans with gallium Ga-68–aGPC3-scFv were safe, well-tolerated, and effective at providing high-contrast images of GPC3-positive liver tumors, making the new immunoPET tracer a potential new tool for the early diagnosis and staging of HCC.
“While current imaging and diagnosis of HCC primarily depend on contrast-enhanced CT or MRI to identify structural changes, PET imaging has the potential to reveal early molecular alterations that precede visible anatomical shifts,” noted Mengting Li, PhD, Attending Physician at the Nuclear Medicine Department of Wuhan Union Hospital, in Wuhan, Hubei, China. “Our study concentrated on imaging glypican-3 (GPC3), a cell surface receptor that is overexpressed in most hepatocellular carcinomas and represents a highly specific target for molecular diagnostics and imaging.”
Study Methods and Rationale
Many HCCs are diagnosed at an advanced stage, leading to poor survival outcomes. Additionally, liver damage and fibrosis due to chronic hepatitis or liver cirrhosis seen in many patients, often make it more challenging to detect tumors when they are still small and manageable.
Clypican-3 (GPC3) is a cell surface receptor that is overexpressed in many hepatocellular carcinomas, but not on normal or cirrhotic liver tissue, making it an attractive target for molecular diagnostics.
The study included 30 patients with suspected HCC who underwent PER/MR scans with Ga-68–aGPC3-scFv. Ga-68–aGPC3-scFv was produced by labeling the antibody fragment precursor with Ga-68 from a generator and achieving a reaction at 37°C for 30 minutes followed by sterile filtration. The imaging was completed in two phases from head to mid-thigh at 30 minutes and 2 and a half hours after administration of Ga-68–aGPC3-scFv. After imaging, all patients underwent surgical pathology to confirm a possible cancer diagnosis.
Study Findings
Administration of Ga-68–aGPC3-scFv was successfully synthesized with radiolabeling yield of more than 85% and a radiochemical purity of more than 99%. No adverse effects were reported with administration.
Biodistribution of the immunoPET was clean at both registered phases. The kidney showed the highest accumulation of Ga-68–aGPC3-scFv over time; hepatic and heart blood pool activity decreased over time. The GPC3-targeted immunoPET was also to detect HCC lesions, including those that were less than 1 cm, with high imaging contrast.
The diagnosis sensitivity was 91.7% and the specificity was 83.3%. The median SUVmax was 17.2 (range, 8.2–51.8), the median tumor-to-liver ratio was 5.9 (range, 5.1–24.7), and the median tumor-to-blood ratio was 12.5 (range, 3.0–57.6) at 2 and a half hours after administration, suggesting the high sensitivity of the tracer.
“GPC3-targeted immunoPET provides clearer, more accurate imaging with high tumor-to-background contrast, enabling earlier diagnosis and better staging,” said Xiaoli Lan, MD, PhD, Chairwoman of the Department of Nuclear Medicine at Wuhan Union Hospital. “For patients, this could mean life-saving interventions at earlier stages, improved treatment planning, and ultimately, higher survival rates. This breakthrough represents a new era in HCC diagnostics, and we are committed to accelerating its global translation, bringing earlier detection and better survival to [patients with] liver cancer worldwide.”
Disclosure: For full disclosures of the study authors, visit jnm.snmjournals.org.
